Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

Objective: To enhance the recognition of necrotizing sialometaplasia (NS) by elucidating its clinical, pathological characteristics and key diagnostic points, providing a basis for the diagnosis and treatment of the disease. Methods: This study has been reviewed and approved by the Medical Ethics Committee, and informed consent has been obtained from patients. Review the data of a patient with NS occurring at the junction of the right soft and hard palate, and comprehensively analyze its diagnostic process based on its clinical manifestations, imaging, and histopathological examination results. And review the relevant literature on the disease. Results: This study describes a 24-year-old male patient with a documented betel nut habit (2 pieces/day for >6 months), who presented with a bone-deep, irregular crateriform ulcer (3 mm × 6 mm × 5 mm) localized to the right hard-soft palate junction. Spiral CT showed a local soft tissue defect with no apparent underlying bone destruction. Histopathology demonstrated chronic inflammation of the mucosal and minor salivary gland tissues, with no evidence of malignancy. A final diagnosis of NS was established. The ulcer healed completely three weeks after initiation of local anti-inflammatory therapy. A literature review indicates that NS is a rare, benign salivary gland disorder, typically occurring at the hard-soft palate junction in middle-aged men (40-60 years). Its etiology remains unclear, but it is widely attributed to salivary lobe infarction following mechanical trauma-induced ischemia. Due to its clinical resemblance to malignancy, it is often misdiagnosed. Treatment entails local anti-inflammatory measures and meticulous wound care aimed at promoting mucosal healing. Conclusion NS is a self-limiting, benign condition that poses a significant diagnostic challenge due to its close clinical simulation of malignancy. Thus, accurate diagnosis requires a combined assessment of clinical presentation, radiological features, and pathological findings. Treatment is predicated based on a conservative strategy with an emphasis on symptomatic management.

OBJECTIVE: To delineate the clinical and genetic features of a Chinese girl harboring a rare de novo variant of SYNGAP1 associated with Mental retardation, autosomal dominant 5 (MRD5), and to conduct a comprehensive genotype-phenotype correlation analysis within the Chinese population through an extensive literature review. METHODS: A 5-year-old girl presenting with seizures without an obvious cause was enrolled in September 2020. Genomic DNA was extracted from the patient and her parents. Whole exome sequencing (WES) was performed on the proband to identify suspected pathogenic variants based on her clinical phenotype. Sanger sequencing was used for validation, followed by bioinformatic analysis of the variant. Additionally, data from 54 previously reported Chinese cases with SYNGAP1 variants were integrated to summarize the distribution of variant types and clinical characteristics. Ethical approval was obtained from the Ethics Committee of Kunming Children's Hospital (Ethics No.: 2021-03-055-K01). RESULTS: WES identified a heterozygous nonsense variant, SYNGAP1 c.725G>A (p.Trp242*), in the proband. Sanger sequencing confirmed it was a de novo variant. According to the ACMG guidelines, this variant was classified as pathogenic (PVS1+PS2). Based on the clinical manifestations, the patient was diagnosed with MRD5. Bioinformatic analysis suggested that this variant introduces a premature stop codon at tryptophan 242, disrupting the PH domain and leading to the loss of the C2, Ras-GAP, and C-terminal domains. The pooled analysis of Chinese cases revealed that nonsense (38.2%) and frameshift (36.4%) variants were the predominant types. Intellectual disability/developmental delay was present in 100.0% of patients, epilepsy in 83.6%, and autism spectrum disorder in 41.3%. The incidence of epilepsy differed significantly among variant types (P = 0.045). Exons 8 and 15 were identified as mutation hotspots. CONCLUSION This study has identified a SYNGAP1 c.725G>A variant in the Chinese population and confirmed it as a potential cause of MRD5, which expanded the mutational spectrum of this disorder.
Humans ; Female ; Child, Preschool ; Intellectual Disability/genetics* ; ras GTPase-Activating Proteins/genetics* ; Phenotype ; Exome Sequencing ; Genetic Association Studies

ObjectiveTo explore the effect of the medical-community linkage model on activities of daily living, psychological status and motor function of stroke patients in the community. MethodsA total of 60 stroke patients admitted to two community health service centers and their affiliated stations in Fengtai District, Beijing, from January, 2024 to August, 2025 were enrolled and randomly divided into control group (n = 30) and intervention group (n = 30). The control group received routine medicine, dietary care and rehabilitation management, while the intervention group underwent rehabilitation with the medical-community linkage model, for twelve weeks. They were assessed with modified Barthel Index (MBI), Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD) and Fugl-Meyer Assessment (FMA) before and after intervention. ResultsAfter intervention, the MBI, HAMA, HAMD and FMA scores of patients improved in both groups (|t| > 5.599, P < 0.001), and improved more in the intervention group than in the control group (P < 0.05), except MBI. The HAMA and HAMD scores of family members decreased in both groups (|t| > 10.333, P < 0.001), and decreased more in the intervention group than in the control group (t > 5.681, P < 0.001). ConclusionThe medical-community linkage model can further improve the motor function of stroke patients in community, as well as the psychological status of both patients and their family members.

ObjectiveTo investigate the mechanism by which Simiao Wan improve intestinal uric acid excretion in hyperuricemic （HUA） rats by inhibiting ferroptosis via the solute carrier family 7 member 11/glutathione peroxidase 4 （SLC7A11/GPX4） signaling pathway. MethodsForty-eight male SD rats were randomly assigned to a normal group， a model group， a low-dose Simiao Wan group （282.6 mg·kg^-1）， a high-dose Simiao Wan group （565.2 mg·kg^-1）， an etoricoxib group （5.4 mg·kg^-1）， and a ferroptosis inhibitor （Fer-1） group （2 mg·kg^-1）. Except for the normal group， rats in all other groups were intraperitoneally injected with potassium oxonate （100 mg·kg^-1） combined with intragastric administration of hypoxanthine （500 mg·kg^-1） to establish the HUA rat model. After 21 days， rats in each administration group received the corresponding dose of drug by gavage， rats in the Fer-1 group received intraperitoneal injection of Fer-1， and rats in the normal and model groups were given an equal volume of normal saline by gavage. After sampling， serum levels of uric acid （SUA）， creatinine （Cr）， and blood urea nitrogen （BUN） were measured using biochemical assays. The content of ferrous ion （Fe²⁺）， reduced glutathione （GSH）， and malondialdehyde （MDA）， as well as superoxide dismutase （SOD） activity in ileal tissues were determined. Hematoxylin and eosin （HE） staining was performed to observe the histopathological changes in the ileum， and transmission electron microscopy was used to observe mitochondrial alterations in the ileal tissue. Immunohistochemistry （IHC） and Western blot were used to detect the protein expression levels of GPX4， ferritin heavy chain 1 （FTH1）， acyl-CoA synthetase long-chain family member 4 （ACSL4）， SLC7A11， and ATP-binding cassette transporter G2 （ABCG2） in ileal tissue. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to determine the mRNA expression of GPX4， FTH1， ACSL4， SLC7A11， and ABCG2 in the ileal tissue. ResultsCompared with the normal group， the model group exhibited significantly elevated serum UA， Cr， and BUN levels （P<0.01）， significantly increased content of MDA and Fe²⁺ in ileal tissue， and significantly decreased GSH content and SOD activity （P<0.01）. HE staining showed extensive shedding of the ileal villous epithelium， disrupted and disorganized villous structure， and incomplete local tissue architecture. Transmission electron microscopy revealed reduced mitochondrial volume， decreased or even vanished cristae， indicating ultrastructural features characteristic of ferroptosis. Molecular and immunohistochemical results demonstrated that the protein and mRNA expression levels of GPX4， FTH1， SLC7A11， and ABCG2 were significantly downregulated， whereas those of ACSL4 were significantly upregulated （P<0.05， P<0.01）. Compared with the model group， after intervention with Simiao Wan， the serum UA， Cr， and BUN levels significantly decreased in all dose groups （P<0.05，P<0.01）， the MDA and Fe²⁺ content in ileal tissues were significantly reduced （P<0.01）， and the GSH content and SOD activity significantly increased （P<0.01）. HE staining showed that the shedding of ileal villous epithelium was markedly alleviated， the villous structure became relatively intact and regularly arranged， and local tissue damage was obviously improved. Transmission electron microscopy showed attenuated mitochondrial damage， improvement in mitochondrial shrinkage， and partial restoration of mitochondrial cristae. Molecular and immunohistochemical results showed that Simiao Wan upregulated GPX4， FTH1， SLC7A11， and ABCG2， and downregulated ACSL4 in a dose-dependent manner. In the high‑dose group， all indices improved significantly （P<0.05，P<0.01）， whereas in the low‑dose group， only improving trends were observed for FTH1， SLC7A11 mRNA， and ABCG2 protein. ConclusionSimiao Wan may inhibit ferroptosis of ileal epithelial cells by regulating the SLC7A11/GPX4 signaling pathway， and upregulate the expression of the uric acid transporter ABCG2， thereby promoting intestinal uric acid excretion and improving HUA.

Objective To explore the effect of the knockdown of transmembrane 9 superfamily protein member 2 (TM9SF2) on the replication of vesicular stomatitis virus (VSV), and investigate its role in the mechanism of antiviral innate immunity. Methods Small interfering RNA (siRNA) was used to knock down the TM9SF2 gene in human non-small cell lung cancer A549 cells. The CCK-8 method was used to assess cell proliferation. A VSV-green fluorescent protein (VSV-GFP) infected cell model was established. The plaque assay was used to measure the viral titer in the supernatant. RT-qPCR and Western blotting were employed to quantify the mRNA and protein levels of VSV genome replication in A549 cells following VSV infection, as well as the expression of interferon β (IFN-β) mRNA and interferon regulatory factor 3 (IRF3) protein phosphorylation following polyinosinic-polycytidylic acid (poly(I:C)) stimulation. Results Compared to the negative control, the knockdown of TM9SF2 exhibited a significant effect, with no observed impact on A549 cell proliferation. The VSV-GFP infected A549 cell model was successfully established. After viral stimulation, fluorescence intensity was reduced following TM9SF2 knockdown, and the mRNA and protein levels of VSV were significantly downregulated. The viral titer of VSV was decreased. After poly(I:C) stimulation, TM9SF2 knockdown significantly upregulated the mRNA level of IFN-β and the phosphorylation level of IRF3 protein. Conclusion The knockdown of TM9SF2 inhibits the replication of vesicular stomatitis virus, and positively regulates the type I interferon signaling pathway, thus enhancing the host's antiviral innate immune response.
Humans ; Virus Replication/genetics* ; Signal Transduction ; Membrane Proteins/metabolism* ; A549 Cells ; Vesiculovirus/physiology* ; Interferon-beta/metabolism* ; Interferon Regulatory Factor-3/genetics* ; Interferon Type I/metabolism* ; Vesicular Stomatitis/immunology* ; Gene Knockdown Techniques ; Vesicular stomatitis Indiana virus/physiology* ; RNA, Small Interfering/genetics*

BACKGROUND: Based on the China-VHD database, this study sought to develop and validate a Valvular Heart Disease- specific Age-adjusted Comorbidity Index (VHD-ACI) for predicting mortality risk in patients with VHD. METHODS & RESULTS: The China-VHD study was a nationwide, multi-centre multi-centre cohort study enrolling 13,917 patients with moderate or severe VHD across 46 medical centres in China between April-June 2018. After excluding cases with missing key variables, 11,459 patients were retained for final analysis. The primary endpoint was 2-year all-cause mortality, with 941 deaths (10.0%) observed during follow-up. The VHD-ACI was derived after identifying 13 independent mortality predictors: cardiomyopathy, myocardial infarction, chronic obstructive pulmonary disease, pulmonary artery hypertension, low body weight, anaemia, hypoalbuminaemia, renal insufficiency, moderate/severe hepatic dysfunction, heart failure, cancer, NYHA functional class and age. The index exhibited good discrimination (AUC, 0.79) and calibration (Brier score, 0.062) in the total cohort, outperforming both EuroSCORE II and ACCI (P < 0.001 for comparison). Internal validation through 100 bootstrap iterations yielded a C statistic of 0.694 (95% CI: 0.665-0.723) for 2-year mortality prediction. VHD-ACI scores, as a continuous variable (VHD-ACI score: adjusted HR (95% CI): 1.263 (1.245-1.282), P < 0.001) or categorized using thresholds determined by the Yoden index (VHD-ACI ≥ 9 vs. < 9, adjusted HR (95% CI): 6.216 (5.378-7.184), P < 0.001), were independently associated with mortality. The prognostic performance remained consistent across all VHD subtypes (aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid valve disease, mixed aortic/mitral valve disease and multiple VHD), and clinical subgroups stratified by therapeutic strategy, LVEF status (preserved vs. reduced), disease severity and etiology. CONCLUSION The VHD-ACI is a simple 13-comorbidity algorithm for the prediction of mortality in VHD patients and providing a simple and rapid tool for risk stratification.

Objective To compare the clinical efficacy of low-molecular-weight heparin anticoagulant drugs in the treatment of venous thrombosis caused by viral pneumonia.Methods The clinical data of 355 patients diagnosed with viral pneumonia patients in the First People's Hospital of Yunnan Province from December 2022 to February 2023 were collected by retrospective analysis.The patients were classified into moderate group(n=1 14),severe group(n=116),and critical group(n=125)based on the severity of viral pneumonia.The changes in coagulation indicators of the patients after treatment with low molecular weight heparin sodium injection,low molecular weight heparin calcium injection,and enoxaparin sodium injection were compared among three groups.Results Compared with before treatment,there was no statistically significant difference in white blood cells count among three groups of patients after treatment(P＞0.05);The hypersensitive C-reactive protein levels of patients in moderate group and critical group decreased(P＜0.05);The levels of D-dimer decreased in severe group and critical group of patients(P＜0.05).After treatment with low-molecular-weight heparin calcium injection,the activated partial thromboplastin and prothrombin time of patients in severe group were shortened compared to before treatment,and the D-dimer levels of patients in severe group and critical group were reduced compared to before treatment,with statistical significance(P＜0.05);After treatment with low-molecular-weight heparin sodium and enoxaparin,only critical group showed a significant decrease in D-dimer levels(P＜0.05).Conclusion Low-molecular-weight heparin calcium injection has a stronger alleviating effect on blood hypercoagulability caused by elevated D-dimer levels than low-molecular-weight heparin sodium and enoxaparin,which is beneficial for relieving patients' hypercoagulability.

The construction of a new cultural system for high-quality development in public hospitals serves as a crucial pillar for achieving their high-quality advancement.During this developmental processe stablishing a cultural framework that aligns with the new development model holds particular significance.Through content analysis methodology,it identifies 18 core elements of the new cultural system for high-quality development in public hospitals.Furthermore it synthesizes seven implementation pathways across three dimensions-organizational patientand employee perspectives:digital leadership organizational reform capability talent innovation capability resource integration capability normative constraint force value co-creation capability and employee support capability.These findings provide both theoretical and practical references for cultivating new cultural constructs that facilitate high-quality development in public hospitals.

Objective:To analyze the prevalence of human respiratory syncytial virus（RSV）and the evolutionary characteristics of the adhesion glycoprotein（G）gene in Xi'an from 2023 to 2024.Methods:Respiratory specimens were collected from patients with acute respiratory infections in Xi'an between October 2023 to October 2024. RSV nucleic acid screening was performed using real-time fluorescence quantitative PCR；full-length G gene sequencing was conducted on nucleic acid-positive specimens. Genotyping characterization of the obtained sequences was performed using Nextclade v3.10.0 software.Results:A total of 2 548 respiratory tract infection samples were collected，with 104 cases（4.08%，104/2 548）testing positive for RSV. The highest RSV positivity rate was observed in children aged ≤1 year（12.24%，18/147），and significant difference in positivity rates were found among age groups（χ 2=37.868， P<0.001）. Since October 2023，RSV has seen an epidemic peak during January to February 2024，and gradually declined thereafter，with no positive cases from May to September 2024. Among the 43 RSV-positive samples，12 strains were identified as subtype A（all genotype A.D.3），and 31 strains were subtype B（14 genotype B.D.4.1.1 and 17 genotype B.D.E.1）. Conclusion:From October 2023 to October 2024，RSV had an epidemic peak in January and February in Xi＇an，with subtype B being the predominant circulating type.